MiR-146
Encyclopedia
miR-146 is a family of microRNA precursors found in mammal
s, including human
s. The ~22 nucleotide
mature miRNA sequence is excised from the precusor hairpin by the enzyme Dicer
. This sequence then associates with RISC
which effects RNA interference
.
miR-146 is primarily involved in the regulation of inflammation
and other process that function in the innate immune system
. Loss of functional miR-146 (and mir-145
) could predispose an individual to suffer from chromosome 5q deletion syndrome. miR-146 has also been reported to be highly upregulated in osteoarthritis
cartilage, and could be involved in its pathogenesis
.
. The expression of miR-146 is upregulated by inflammatory factors such as interleukin 1 and tumor necrosis factor-alpha. miR-146 dysregulates a number of targets which are mostly involved in toll-like receptor
pathways that bring about a cytokine
response as part of the innate immune system. miR-146 operates in a feedback system or "negative regulatory loop" to finely tune inflammatory responses.
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s, including human
Human
Humans are the only living species in the Homo genus...
s. The ~22 nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
mature miRNA sequence is excised from the precusor hairpin by the enzyme Dicer
Dicer
Dicer is an endoribonuclease in the RNase III family that cleaves double-stranded RNA and pre-microRNA into short double-stranded RNA fragments called small interfering RNA about 20-25 nucleotides long, usually with a two-base overhang on the 3' end...
. This sequence then associates with RISC
RNA-induced silencing complex
RNA-Induced Silencing Complex, or RISC, is a multiprotein complex that incorporates one strand of a small interfering RNA or micro RNA . RISC uses the siRNA or miRNA as a template for recognizing complementary mRNA. When it finds a complementary strand, it activates RNase and cleaves the RNA...
which effects RNA interference
RNA interference
RNA interference is a process within living cells that moderates the activity of their genes. Historically, it was known by other names, including co-suppression, post transcriptional gene silencing , and quelling. Only after these apparently unrelated processes were fully understood did it become...
.
miR-146 is primarily involved in the regulation of inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
and other process that function in the innate immune system
Innate immune system
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...
. Loss of functional miR-146 (and mir-145
Mir-145
In molecular biology mir-145 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by a several mechanisms.-Targets:MicroRNAs are involved in down regulation of a variety of target genes. Götte et al...
) could predispose an individual to suffer from chromosome 5q deletion syndrome. miR-146 has also been reported to be highly upregulated in osteoarthritis
Osteoarthritis
Osteoarthritis also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion...
cartilage, and could be involved in its pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
.
Function
miR-146 is thought to be a mediator of inflammation along with another microRNA, mir-155Mir-155
MicroRNAs are non-coding RNAs that regulate the expression levels of other genes through several mechanisms at a post transcriptional stage, they work by inactivating translation of gene or gene clusters or by degrading genes...
. The expression of miR-146 is upregulated by inflammatory factors such as interleukin 1 and tumor necrosis factor-alpha. miR-146 dysregulates a number of targets which are mostly involved in toll-like receptor
Toll-like receptor
Toll-like receptors are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors that recognize structurally conserved molecules derived from microbes...
pathways that bring about a cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
response as part of the innate immune system. miR-146 operates in a feedback system or "negative regulatory loop" to finely tune inflammatory responses.